The role played by glycosaminoglycan hyaluronate (HA) in normal and abnormal morphogenesis of the mouse lip and primary palate will be investigated. Emphasis will be placed on correlating levels of HA in the extracellular matrix (ECM) of the developing nasal processes with the morphology and behavior of associated mesenchyme cells. First, glycosaminoglycans present in the ECM will be identified and localized histochemically. Synthesis of HA, as measured by incorporation of labeled glucosamine, will be monitored at successive stages of nasal process outgrowth. The effect of HA removal on nasal process formation will be studied using a model system in which mouse embryos, maintained in whole embryo culture, are exposed to Streptomyces hyaluronidase. This enzyme degrades HA specifically. Control and hyaluronidase-treated embryos will be compared with respect to several types of cell behavior, including shape changes, proliferation and movement. Specifically, surface morphology, ultrastructure, and relationships of facial mesenchyme cells will be observed by scanning and transmission electron microscopy. Cellular proliferation, as measured by thymidine labeling indices, will be analyzed statistically. And, the possible contribution of mesenchyme cell movement to nasal process outgrowth and the effect of HA removal on this phenomenon will be investigated using a cell marking technique. The proposed studies should facilitate identification of potential teratogenic mechanisms involved in cleft lip formation.